EMA Clears Investigator-Initiated Phase 1b/2 Trial of LP-184 in Biomarker-Selected Advanced Bladder Cancer

Lantern Pharma has received clearance from the European Medicines Agency (EMA) to begin an investigator-initiated Phase 1b/2 clinical trial evaluating its investigational precision oncology therapy LP-184 (zirdafulven) in patients with advanced or metastatic urothelial carcinoma. The study will be conducted at Rigshospitalet in Copenhagen, Denmark, in collaboration with Professor Helle Pappot, MD, DMSc, and will enroll patients whose disease has progressed after, or who are ineligible for, current standard treatments.

The trial is among the first prospective studies in advanced bladder cancer to use a dual biomarker approach, selecting patients whose tumors overexpress prostaglandin reductase 1 (PTGR1) and harbor deficiencies in DNA damage repair pathways, particularly nucleotide excision repair (NER). Lantern believes this strategy could identify patients most likely to benefit from LP-184, an investigational small-molecule therapy with a synthetic-lethal mechanism of action.

Precision Oncology Strategy Targets an Unmet Need

Bladder cancer remains one of the ten most common cancers worldwide, with approximately 550,000 new diagnoses annually. An estimated 84,500 new cases are expected in the United States during 2026. Despite advances such as first-line treatment with enfortumab vedotin plus pembrolizumab, patients who progress beyond standard therapies have limited options and poor clinical outcomes.

Lantern estimates that approximately 20% to 25% of bladder cancer patients ultimately require third-line treatment, representing more than 130,000 patients globally each year and a potential market opportunity exceeding $3 billion by 2035.

Real-world evidence from the multicenter STATES-Bladder study published in Urologic Oncology showed that only 25% of patients with metastatic urothelial cancer reached third-line therapy, while just 6% received fourth-line treatment, underscoring the need for more effective later-line therapies.

 LP-184 Exploits Synthetic-Lethal Biology

LP-184 is an investigational acylfulvene-class prodrug activated by PTGR1, an enzyme frequently overexpressed in urothelial tumors and associated with poor prognosis. Following activation, the drug induces DNA damage that relies primarily on the nucleotide excision repair pathway for repair.

Tumors carrying NER deficiencies, including alterations in ERCC genes, cannot effectively repair this damage, creating a synthetic-lethal vulnerability. Coexisting homologous recombination defects may further increase tumor sensitivity. Approximately 10% to 15% of metastatic urothelial cancers harbor NER alterations, while PTGR1 overexpression is common in this disease.

Currently, no FDA-approved therapy specifically targets NER-deficient tumors.

Phase 1b/2 Study Will Evaluate Safety and Antitumor Activity

The open-label trial will enroll up to approximately 39 patients with recurrent or metastatic urothelial carcinoma.

The Phase 1b portion will use a dose-optimization approach beginning near the anticipated therapeutic dose based on results from Lantern’s completed multi-tumor Phase 1a study (NCT05933265). Patients treated at the selected dose will transition directly into the Phase 2 expansion.

The Phase 2 study will use a Simon two-stage design, with objective response rate assessed by RECIST 1.1 as the primary endpoint. Secondary and exploratory endpoints include progression-free survival, overall survival, duration of response, patient-reported quality of life, and correlations between PTGR1 and DNA damage repair biomarkers and clinical outcomes.

AI-Guided Development Strategy

Lantern President and Chief Executive Officer Panna Sharma said the study reflects the company’s biomarker-guided development strategy enabled by its proprietary RADR® artificial intelligence platform. He noted that the collaboration with Rigshospitalet provides an opportunity to evaluate LP-184 in a biomarker-selected urothelial cancer population while supporting the broader clinical development program.

LP-184 has previously received FDA Fast Track and Orphan Drug designations in multiple indications, including triple-negative breast cancer. The company is also advancing the investigational therapy across additional solid tumors and central nervous system cancers using AI-driven biomarker selection strategies.

The EMA-cleared European trial adds another clinical evaluation of LP-184 and may help define the role of dual biomarker-guided precision medicine in advanced bladder cancer, an area where treatment options remain limited after standard therapies fail.

Reference

Lantern Pharma Inc – Lantern Pharma to Advance EMA-Cleared Phase 1b/2 Trial of LP-184 (Zirdafulven) in Biomarker-Selected Advanced Bladder Cancer